The small airway disease in asthma is characterized by airway wall thickening associated with eosinophilic inflammation and hypervascularity. In our study, predicted forced expiratory volume in 1 s (% FEV₁) correlated with the vascularity in the inner layers of large airways but not for small airways. High-resolution computed tomography (CT) scans of 0.5 mm collimation during acute mild exacerbations revealed mucus plugging, air-space nodules and ground-glass opacities. Mean lung density on CT in acute exacerbations was significantly increased compared with that in remission. These results suggest that the involvement of the small airways and lung parenchyma would be increased during exacerbations. Pathologically, eosinophils were significantly reduced by treatment with chlorofluorocarbon-beclomethasone dipropionate (BDP) in the large airways, but not in the small airways. New fine-particle inhaled corticosteroids (ICS), such as hydrofluoroalkane-BDP, can reach the small airways and lung parenchyma in asthmatic patients. From the results of peak inspiratory flow (PIF) through each dry powder inhaler in Japanese people, measurement of PIF should be recommended before the use of dry powder inhaler. In the present review, we address small airway disease in asthmatic patients using pathological and radiological methods and discuss the critical problems of current ICS therapy.

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Collagen-vascular diseases (CVD) involve many organs. Among organ involvements, pulmonary disorders may determine the prognosis of CVD. Because the vasculature and blood perfusion are commonly altered in CVD, we have attempted to analyze pulmonary disorders from the viewpoint of pulmonary vessels and perfusion. Based on routine pulmonary function tests, many patients were observed to have a decreased diffusion capacity (DLco) isolated from or comparative to lung volumes. In these patients, matched ventilation/perfusion scintigraphy revealed a decrease in pulmonary peripheral perfusion. These findings may be an early sign of pulmonary hypertension, which develops as a result of several pathophysiological causes in CVD. When a remedy for each pathogenesis of pulmonary hypertension was applied, more than half the patients recovered, at least initially; therefore, early diagnosis, including the methods described above, and treatment are important. With regard to pneumonitis in amyopathic dermatomyositis, which has been considered to develop acutely, we observed its progression to be subacute in its early stage. Along with this disease, pneumomediastinum characteristically develops simultaneously with vasculopathy. Disease-modifying antirheumatic drugs, which must be perfused into the blood stream, sometimes induce lymphocyte alveolitis or pneumonitis in good responders, with a decrease in the peripheral blood lymphocyte count and immunoglobulin levels. Examinations, differential diagnoses, therapies and studies from the viewpoint of the blood circulation and vessels may be important and useful for clinical studies and for the further investigation of pulmonary involvement in CVD.

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Theophylline is a bronchodilator that also has an anti-inflammatory effect. In Japan, methylxanthines, including theophylline and aminophylline (theophylline ethylenediamine), have been used widely in the treatment of asthma. In some asthma management guidelines, although methylxanthines are recommend for the treatment of asthma, they are not preferred primarily because of potential serious adverse effects in case of overdose. The present review examines the efficacy and adverse effects of sustained-release theophylline and injectable methylxanthines in the treatment of chronic asthma and acute exacerbation of asthma by evaluating reports of published clinical trials and a prospective survey on the occurrence of serious adverse drug reactions to these agents. A prospective survey on the safety of methylxanthines was administered to adult patients (15-64 years of age), mainly with asthma, in medical centers by physicians certified as specialists by the Japanese Society of Allergology. Review of published clinical trials has shown that methylxanthines are effective in controlling asthma. In the prospective study, in the case of sustained-release theophylline, 3921subjects reported by 66 medical centers and meeting the criteria for inclusion in the survey were selected for analysis. In the case of intravenous methylxanthines, 682 subjects reported by 55 medical centers conforming and meeting the criteria for inclusion in the survey were selected for analysis. None of these subjects exhibited serious adverse drug reaction with sustained-release theophylline or intravenous methylxanthines. In conclusion, methylxanthines are effective for the treatment of asthma and are safe as long as the dose administered accords with the protocols recommended by asthma management guidelines.

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Background: Reactivation of human herpesvirus (HHV) infection, especially HHV-6, has been observed in patients with drug-induced hypersensitivity syndrome (DIHS). In toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), the relevance of HHV infection to the symptoms is unclear.
Methods: Patients with a diagnosis of DIHS (n=7), TEN (n=5) and SJS (n=4) were included in the present study. These patients were evaluated for the presence of active HHV-6, HHV-7 and cytomegalovirus (CMV) infections by serological tests and polymerase chain reaction with blood.
Results: More than 3 weeks after the onset of DIHS, HHV-6 serological tests revealed a remarkable rise in IgG antibodies in six patients, including one treated without steroids. Human herpesvirus-6 DNA was detected in blood from three patients. In one patient with DIHS, reactivation of CMV was shown without reactivation of HHV-6, whereas in three patients anti-CMV IgG antibodies increased after the rise of anti-HHV-6 IgG antibodies. Anti-HHV-7 IgG antibodies did not show remarkable rises in any of these patients. As for patients with TEN and SJS, anti-HHV-6, anti-HHV-7 and anti-CMV IgG antibodies showed no significant increase, except for one patient in whom anti-HHV-6 and anti-HHV-7 IgG antibodies increased, but not more than 1 : 160, after steroid therapy. Human herpesvirus-6 DNA was not detected in the blood of those patients.
Conclusions: Human herpesvirus-6 reactivation in patients with DIHS is not due to non-specific reactivation induced by steroid therapy, but to events specific to DIHS. We hypothesize that DIHS may occur as a result of reactivation of HHV, especially HHV-6, accompanied with an allergic reaction to drugs, followed by a substantial immune response to the virus that is probably responsible for visceral involvement.

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